The major goal of this renewal proposal is to pursue studies on the mechanism(s) of cleft palate production by corticosteroids and other drugs at biochemical and molecular (receptor) level. We plan to extend our previous observations that the susceptibility of various strains of mice to cortisone induced cleft palate is correlated with the level of a cytosolic corticoid binding protein in palatal anlagen and the H-2 locus strongly regulates the amount of this protein. We propose to test this hypothesis of cleft palate inducing agents by using our two newly developed in vitro model systems of human and mice (inbred strains) fetal palatal cell and shelf cultures. Finally, at the biochemical level we plan to investigate the role of corticosteroids and other teratogens in the programmed cell death of medial edge palatal epithelium by inhibition of lysosomal membrane breakdown as a mechanism of teratogenesis.